The microbiome – next frontier in tackling disease?

What is the microbiome?

An enormous collective community of different micro-organisms (microbiota), such as viruses, bacteria, and forms of fungi live in and on the human body. Since the time of Pasteur we have been interested in the function of these organisms and have argued over the role they play in health and disease. Now, advances in technologies such as high-throughput DNA sequencing, metagenomics (analysis of uncultured microbes sampled directly from their habitats) and bioinformatics are allowing us to begin to uncover the role of these organisms.

Microbiota and the microbiome (genetic material within a microbiota) are an attractive target for those interested in personalised healthcare for two major reasons. Firstly, they are unique to individuals but have functions that are conserved across individuals, a characteristic that is similar to the genome and which means they can serve as an additional source of biomarkers for early disease detection. And, they can be manipulated - which means that unlike the genome they serve as a potentially modifiable risk factor, which can be used in disease prevention and treatment.

Tackling disease

Almost every study attempting to correlate the microbiome with specific diseases (e.g. obesity, asthma, malnutrition, behaviour) has been successful. By this I mean that a number of research studies have linked changes in the microbiome to specific diseases. The positive message from these studies is that it highlights the important role that the microbiome plays in human biology. However, most of these studies do not untangle whether these changes are causal or a consequence of disease and unless we know the direction of the effect, the role of the microbiome as disease biomarker remains limited.

Interpretation is further complicated by the fact that the microbiome is in constant flux. For example, many companies and individuals are promoting the maintenance of a “healthy” microbiome as a way to optimise your health. Intuitively this makes sense, the problem we face is that is that we are still unclear what a “healthy” microbiome is and in some cases an “unhealthy” microbiome can be normal, such as in the case of pregnant women in their third trimester of pregnancy, whose microbiomes resemble that of people with metabolic syndrome.

Unpicking the role of microbiota in health and disease is not a simple task given the complex nature of microbial communities and our limited understanding of the complex relationship between microbial species, their function and their products along with the interaction of these elements with the host. Many are coming to view the human body as an ecosystem in constant flux with environmental influences throughout life having an impact on microbial composition. At the moment we are limited by the lack of appropriate methods available to understand such a dynamic system in order to develop useful tools for healthcare.

The bottom line

There are few examples, barring faecal microbiota transplants (FMT), where microbiota analysis and manipulation have been successfully applied within healthcare. Even with FMT, it is only recommended for use in treatment in severe cases of recurrent clostridium difficile infections (CDI) as there are concerns about what the long-term health impact that changes in microbiota may have on patients.

In our view, the science of the microbiome is still in a discovery phase, some way from mainstream impact on healthcare, and there remain many unanswered questions still to be addressed about how to achieve such impact in the future.

It is unlikely that microbiome analysis will ever be useful in isolation as a tool to improving health. Instead, if it is used as part of an integrated approach to personalising healthcare that leverages knowledge about a wider range of biomarkers, it may in time prove useful. Realising this goal is almost certain to require a significant shift away from the current healthcare paradigm of treating individual body systems in isolation towards taking a whole person approach to understanding health and disease, not something that will be achieved easily.